The FDA-Approved Oral Drug Nitazoxanide Amplifies Host Antiviral Responses and Inhibits Ebola Virus
Summary: Here, we show that the US Food and Drug Administration-approved oral drug nitazoxanide (NTZ) broadly amplifies the host innate immune response to viruses and inhibits Ebola virus (EBOV) replication. We find that NTZ enhances retinoic-acid-inducible protein I (RIG-I)-like-receptor, mitochond...
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doaj-9f3da93723f94426a367b10802819d642020-11-24T21:34:05ZengElsevieriScience2589-00422019-09-011912791290The FDA-Approved Oral Drug Nitazoxanide Amplifies Host Antiviral Responses and Inhibits Ebola VirusLuke D. Jasenosky0Cristhian Cadena1Chad E. Mire2Viktoriya Borisevich3Viraga Haridas4Shahin Ranjbar5Aya Nambu6Sina Bavari7Veronica Soloveva8Supriya Sadukhan9Gail H. Cassell10Thomas W. Geisbert11Sun Hur12Anne E. Goldfeld13Program in Cellular and Molecular Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USAProgram in Cellular and Molecular Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USADepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USAProgram in Cellular and Molecular Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USAProgram in Cellular and Molecular Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USAProgram in Cellular and Molecular Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USAU.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USAU.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USAProgram in Cellular and Molecular Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USADepartment of Global Health and Social Medicine, Harvard Medical School, Boston, MA 02115, USADepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USAProgram in Cellular and Molecular Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USAProgram in Cellular and Molecular Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA; Infectious Disease Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Corresponding authorSummary: Here, we show that the US Food and Drug Administration-approved oral drug nitazoxanide (NTZ) broadly amplifies the host innate immune response to viruses and inhibits Ebola virus (EBOV) replication. We find that NTZ enhances retinoic-acid-inducible protein I (RIG-I)-like-receptor, mitochondrial antiviral signaling protein, interferon regulatory factor 3, and interferon activities and induces transcription of the antiviral phosphatase GADD34. NTZ significantly inhibits EBOV replication in human cells through its effects on RIG-I and protein kinase R (PKR), suggesting that it counteracts EBOV VP35 protein's ability to block RIG-I and PKR sensing of EBOV. NTZ also inhibits a second negative-strand RNA virus, vesicular stomatitis virus (VSV), through RIG-I and GADD34, but not PKR, consistent with VSV's distinct host innate immune evasion mechanisms. Thus, NTZ counteracts varied virus-specific immune evasion strategies by generally enhancing the RNA sensing and interferon axis that is triggered by foreign cytoplasmic RNA exposure, and holds promise as an oral therapy against EBOV. : Mechanism of Action; Pathogenic Organism; Immune Response; Viral Microbiology Subject Areas: Mechanism of Action, Pathogenic Organism, Immune Response, Viral Microbiologyhttp://www.sciencedirect.com/science/article/pii/S2589004219302287 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Luke D. Jasenosky Cristhian Cadena Chad E. Mire Viktoriya Borisevich Viraga Haridas Shahin Ranjbar Aya Nambu Sina Bavari Veronica Soloveva Supriya Sadukhan Gail H. Cassell Thomas W. Geisbert Sun Hur Anne E. Goldfeld |
spellingShingle |
Luke D. Jasenosky Cristhian Cadena Chad E. Mire Viktoriya Borisevich Viraga Haridas Shahin Ranjbar Aya Nambu Sina Bavari Veronica Soloveva Supriya Sadukhan Gail H. Cassell Thomas W. Geisbert Sun Hur Anne E. Goldfeld The FDA-Approved Oral Drug Nitazoxanide Amplifies Host Antiviral Responses and Inhibits Ebola Virus iScience |
author_facet |
Luke D. Jasenosky Cristhian Cadena Chad E. Mire Viktoriya Borisevich Viraga Haridas Shahin Ranjbar Aya Nambu Sina Bavari Veronica Soloveva Supriya Sadukhan Gail H. Cassell Thomas W. Geisbert Sun Hur Anne E. Goldfeld |
author_sort |
Luke D. Jasenosky |
title |
The FDA-Approved Oral Drug Nitazoxanide Amplifies Host Antiviral Responses and Inhibits Ebola Virus |
title_short |
The FDA-Approved Oral Drug Nitazoxanide Amplifies Host Antiviral Responses and Inhibits Ebola Virus |
title_full |
The FDA-Approved Oral Drug Nitazoxanide Amplifies Host Antiviral Responses and Inhibits Ebola Virus |
title_fullStr |
The FDA-Approved Oral Drug Nitazoxanide Amplifies Host Antiviral Responses and Inhibits Ebola Virus |
title_full_unstemmed |
The FDA-Approved Oral Drug Nitazoxanide Amplifies Host Antiviral Responses and Inhibits Ebola Virus |
title_sort |
fda-approved oral drug nitazoxanide amplifies host antiviral responses and inhibits ebola virus |
publisher |
Elsevier |
series |
iScience |
issn |
2589-0042 |
publishDate |
2019-09-01 |
description |
Summary: Here, we show that the US Food and Drug Administration-approved oral drug nitazoxanide (NTZ) broadly amplifies the host innate immune response to viruses and inhibits Ebola virus (EBOV) replication. We find that NTZ enhances retinoic-acid-inducible protein I (RIG-I)-like-receptor, mitochondrial antiviral signaling protein, interferon regulatory factor 3, and interferon activities and induces transcription of the antiviral phosphatase GADD34. NTZ significantly inhibits EBOV replication in human cells through its effects on RIG-I and protein kinase R (PKR), suggesting that it counteracts EBOV VP35 protein's ability to block RIG-I and PKR sensing of EBOV. NTZ also inhibits a second negative-strand RNA virus, vesicular stomatitis virus (VSV), through RIG-I and GADD34, but not PKR, consistent with VSV's distinct host innate immune evasion mechanisms. Thus, NTZ counteracts varied virus-specific immune evasion strategies by generally enhancing the RNA sensing and interferon axis that is triggered by foreign cytoplasmic RNA exposure, and holds promise as an oral therapy against EBOV. : Mechanism of Action; Pathogenic Organism; Immune Response; Viral Microbiology Subject Areas: Mechanism of Action, Pathogenic Organism, Immune Response, Viral Microbiology |
url |
http://www.sciencedirect.com/science/article/pii/S2589004219302287 |
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